Activity of LY333328 in experimental meningitis caused by a Streptococcus pneumoniae strain susceptible to penicillin.

In a rabbit model of Streptococcus pneumoniae meningitis single doses of 10 and 2.5 mg of the glycopeptide LY333328 per kg of body weight reduced bacterial titers in cerebrospinal fluid (CSF) almost as rapidly as ceftriaxone at 10 mg/kg/h (changes in log CFU, -0.29 +/- 0.21 and -0.26 +/- 0.22 versus -0.34 +/- 0.15/ml/h). A dose of 1 mg/kg was bacteriostatic (change in log CFU, 0.01 +/- 0.11/ml/h). In two animals receiving LY333328 at a dose of 40 mg/kg the bacterial titers were reduced by 0.54 and 0.51 log CFU/ml/h. The penetration of CSF by LY333328 was 1 to 5%. The concentrations of lipoteichoic and teichoic acids in CSF and neuronal damage were similar in ceftriaxone- and LY333328-treated animals.

Recent dioxin contamination from Agent Orange in residents of a southern Vietnam city.

Marked elevation of dioxin associated with the herbicide Agent Orange was recently found in 19 of 20 blood samples from persons living in Bien Hoa, a large city in southern Vietnam. This city is located near an air base that was used for Agent Orange spray missions between 1962 and 1970. A spill of Agent Orange occurred at this air base more than 30 years before blood samples were collected in 1999. Samples were collected, frozen, and sent to a World Health Organization--certified dioxin laboratory for congener-specific analysis as part of a Vietnam Red Cross project. Previous analyses of more than 2200 pooled blood samples collected in the 1990s identified Bien Hoa as one of several southern Vietnam areas with persons having elevated blood dioxin levels from exposure to Agent Orange. In sharp contrast to this study, our previous research showed decreasing tissue dioxin levels over time since 1970. Only the dioxin that contaminated Agent Orange, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was elevated in the blood of 19 of 20 persons sampled from Bien Hoa. A comparison, pooled sample from 100 residents of Hanoi, where Agent Orange was not used, measured blood TCDD levels of 2 parts per trillion (ppt). TCDD levels of up to 271 ppt, a 135-fold increase, were found in Bien Hoa residents. TCDD contamination was also found in some nearby soil and sediment samples. Persons new to this region and children born after Agent Orange spraying ended also had elevated TCDD levels. This TCDD uptake was recent and occurred decades after spraying ended. We hypothesize that a major route of current and past exposures is from the movement of dioxin from soil into river sediment, then into fish, and from fish consumption into people.

Polychlorinated dibenzodioxins and dibenzofurans in butter from different states in Australia.

Nine samples of butter from producers in various states of Australia were analysed for polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Detectable concentrations of 2,3,7,8-chlorine substituted PCDD/Fs were found in all samples. The mean PCDD/F concentration expressed as 2,3,7,8-TCDD equivalents (TEQs) was 0.19 pg TEQ g-1 fat. The highest concentration (0.46 pg TEQ g-1 fat) was observable in a sample from Victoria which is the most densely populated state. Overall the results indicate that PCDD/F concentrations in dairy products from Australia are low in comparison to the levels in dairy products of industrialized countries on the Northern Hemisphere. As expected, this study provides evidence that the environmental and consequently the human body burden of PCDD/Fs to be relatively low in Australia.

D- and L-lactate in rabbit and human bacterial meningitis.

Increased total CSF lactate is an important indicator differentiating bacterial from aseptic meningitis. Bacteria can produce D- and L-lactate; mammalian cells produce only L-lactate. We measured D- and L-lactate production of Streptococcus pneumoniae, Staphylococcus aureus, Neisseria meningitidis and Escherichia coli in vitro, of S. pneumoniae and E. coli in rabbit experimental meningitis and of various common pathogens in CSF from patients with bacterial meningitis. Despite marked in vitro production of D-lactate by S. aureus (maximum: 4.59 mmol/l; i.e. 34.9% of total lactate), N. meningitidis (4.62 mmol/l; i.e. 98.1%) and E. coli (3.14 mmol/l; i.e. 97.2%), minimal amounts were measured in human S. aureus (0.38 mmol/l; i.e. 1.3% of total lactate) or N. meningitidis (0.28 mmol/l; i.e. 3.9%) and experimental E. coli meningitis (0.75 mmol/l; i.e. 4.4%). In only 9 of 54 human CSF samples did D-lactate exceed 0.15 mmol/l. S. pneumoniae did not produce significant amounts of D-lactate in vitro (maximum: 0.55 mmol/l; i.e. 2.7% of total lactate), in experimental meningitis (0.18 mmol/l; i.e. 3%) or in human cases of meningitis (0.28 mmol/l; i.e. 1.9%). In conclusion, increased total CSF lactate in meningitis consists mainly of L-lactate and originates predominantly from host cells. CSF D-lactate is of limited diagnostic value.

Immunoblotting of pollen proteins: Tween 20 mediates nonspecific binding of gammaglobulins to immunoblots of oak-pollen proteins.

Oak-pollen extracts, separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrophoretically transferred onto nitrocellulose, demonstrated extensive banding in the absence of human sera or with nonatopic sera with both a horseradish peroxidase-conjugated goat antihuman IgE and 125I-labeled rabbit antihuman IgE. When the nonionic detergent Tween 20 was removed from all incubations and washes, negative banding appeared, corresponding to bands that were clearly visible when Tween 20 had been used as a blocking agent. When Tween 20 was reintroduced, the bands reappeared. These results demonstrate that, although Tween 20 is effective in blocking unbound sites on nitrocellulose membranes, this and other nonionic detergents may cause nonspecific binding to immunoblots of oak-pollen proteins. Thus, care must be used in the interpretation of immunoblots to detect allergens when Tween 20 is used as the blocking agent.